Korean J Radiol.  2014 Oct;15(5):591-604. 10.3348/kjr.2014.15.5.591.

Intratumoral Heterogeneity of Breast Cancer Xenograft Models: Texture Analysis of Diffusion-Weighted MR Imaging

• Yun BL
• Cho N
• Li M
• Jang MH
• Park SY
• Kang HC
• Kim B
• Song IC
• Moon WK

• KMID: 1734944
• DOI: http://doi.org/10.3348/kjr.2014.15.5.591

Abstract

OBJECTIVE
To investigate whether there is a relationship between texture analysis parameters of apparent diffusion coefficient (ADC) maps and histopathologic features of MCF-7 and MDA-MB-231 xenograft models.
MATERIALS AND METHODS
MCF-7 estradiol (+), MCF-7 estradiol (-), and MDA-MB-231 xenograft models were made with approval of the animal care committee. Twelve tumors of MCF-7 estradiol (+), 9 tumors of MCF-7 estradiol (-), and 6 tumors in MDA-MB-231 were included. Diffusion-weighted MR images were obtained on a 9.4-T system. An analysis of the first and second order texture analysis of ADC maps was performed. The texture analysis parameters and histopathologic features were compared among these groups by the analysis of variance test. Correlations between texture parameters and histopathologic features were analyzed. We also evaluated the intraobserver agreement in assessing the texture parameters.
RESULTS
MCF-7 estradiol (+) showed a higher standard deviation, maximum, skewness, and kurtosis of ADC values than MCF-7 estradiol (-) and MDA-MB-231 (p < 0.01 for all). The contrast of the MCF-7 groups was higher than that of the MDA-MB-231 (p = 0.004). The correlation (COR) of the texture analysis of MCF-7 groups was lower than that of MDA-MB-231 (p < 0.001). The histopathologic analysis showed that Ki-67mean and Ki-67diff of MCF-7 estradiol (+) were higher than that of MCF-7 estradiol (-) or MDA-MB-231 (p < 0.05). The microvessel density (MVD)mean and MVDdiff of MDA-MB-231 were higher than those of MCF-7 groups (p < 0.001). A diffuse-multifocal necrosis was more frequently found in MDA-MB-231 (p < 0.001). The proportion of necrosis moderately correlated with the contrast (r = -0.438, p = 0.022) and strongly with COR (r = 0.540, p = 0.004). Standard deviation (r = 0.622, r = 0.437), skewness (r = 0.404, r = 0.484), and kurtosis (r = 0.408, r = 0.452) correlated with Ki-67mean and Ki-67diff (p < 0.05 for all). COR moderately correlated with Ki-67diff (r = -0.388, p = 0.045). Skewness (r = -0.643, r = -0.464), kurtosis (r = -0.581, r = -0.389), contrast (r = -0.473, r = -0.549) and COR (r = 0.588, r = 0.580) correlated with MVDmean and MVDdiff (p < 0.05 for all).
CONCLUSION
The texture analysis of ADC maps may help to determine the intratumoral spatial heterogeneity of necrosis patterns, amount of cellular proliferation and the vascularity in MCF-7 and MDA-MB-231 xenograft breast cancer models.

Keyword

Animal; Breast neoplasms; Diffusion magnetic resonance imaging; Image interpretation; Computer-assisted

MeSH Terms

Animals
Breast Neoplasms/metabolism/pathology/*radiography
Cell Line, Tumor
*Diffusion Magnetic Resonance Imaging
Estradiol/metabolism
Female
Humans
Image Interpretation, Computer-Assisted
Immunohistochemistry
Ki-67 Antigen/metabolism
MCF-7 Cells
Mice
Mice, Nude
Transplantation, Heterologous
Estradiol
Ki-67 Antigen

Figure

• 

  Fig. 1 Box-and-whisker plot of volumes and first order texture analysis parameters of tumor groups. (A) Volume, (B) mean, (C) median, (D) standard deviation, (E) maximum, (F) minimum, (G) skewness, and (H) kurtosis of ADC maps for MCF-7 estradiol (+) (dark grey boxes), MCF-7 estradiol (-) (light grey boxes) and MDA-MB-231 (white boxes) groups. *Statistical significance with p < 0.05, **Statistical significance with p < 0.01, ***Statistical significance with p < 0.001. ○: observations 1.5 interquartile ranges (IQRs) from end of box, ★: observations 3 IQRs from end of box. ADC = apparent diffusion coefficient

• 

  Fig. 2 Box-and-whisker plot of second order texture analysis parameters of tumor groups. (A) Contrast, (B) entropy, (C) homogeneity, (D) uniformity, and (E) correlation of ADC maps are shown for MCF-7 estradiol (+) (dark grey boxes), MCF-7 estradiol (-) (light grey boxes), and MDA-MB-231 (white boxes) groups. *Statistical significance with p < 0.05, **Statistical significance with p < 0.01, ***Statistical significance with p < 0.001. ○: observations 1.5 interquartile ranges (IQRs) from end of box, ★: observations 3 IQRs from end of box. ADC = apparent diffusion coefficient

• 

  Fig. 3 Box-and-whisker plot of histopathologic features of tumor groups. (A) Proportion of necrosis, (B) Ki-67mean, (C) Ki-67diff (highest-lowest), (D) MVDmean, and (E) MVDdiff (highest-lowest) for MCF-7 estradiol (+) (dark grey boxes), MCF-7 estradiol (-) (light grey boxes), and MDA-MB-231 (white boxes) groups are shown. *Statistical significance with p < 0.05, **Statistical significance with p < 0.01, ***Statistical significance with p < 0.001. ○: observations 1.5 interquartile ranges (IQRs) from end of box, ★: observations 3 IQRs from end of box. HPF = high power field, MVD = microvessel density

• 

  Fig. 4 Relationship between ADC maps and histopathological results. Photomicrographs of entire section show (A) central necrosis (arrows) in MCF-7 estradiol (+) tumor and (B) diffuse multifocal necrosis (arrows) in MDA-MB-231 tumor (H&E, × 1.25). Photomicrographs of immunohistochemical staining show high Ki-67 expression in MCF-7 estradiol (+) tumors (C) and MDA-MB-231 tumors (× 200) (D). Photomicrographs of immunohistochemical staining for CD34 show low microvessel density in MCF-7 estradiol (+) tumors (E) and high microvessel density in MDA-MB-231 tumors (× 200) (F). ADC map (G) shows high ADC values in central necrotic portion (arrows) and (H) spotty high ADC values (arrows) corresponding to necrosis. ADC = apparent diffusion coefficient, H&E = hematoxylin and eosin

• 

  Fig. 5 Relationship between texture parameters and Ki-67 index of tumor groups. (A) Ki-67mean and (B) Ki-67diff showed positive correlation with standard deviation, skewness and kurtosis of ADC texture parameters. However, COR of ADC map showed inverse correlation with Ki-67diff. ADC = apparent diffusion coefficient, COR = correlation

• 

  Fig. 6 Relationship between texture parameters and MVD of tumor groups. (A) MVDmean and (B) MVDdiff showed inverse correlation with skewness, kurtosis and contrast. COR of ADC map correlated with MVDmean and MVDdiff. ADC = apparent diffusion coefficient, COR = correlation, HPF = high power field, MVD = microvessel density

• 

  Fig. 7 Three simulations of different correlations. First-order texture parameters are identical for three cases with mean = 1.5 and standard deviation = 0.5 in all matrices. However, second-order texture parameters derived from grey level co-occurrence matrix varied. A. Most heterogeneous mosaic pattern matrix shows lowest correlation value -0.09. B. Intermediate pattern shows correlation 0.49. C. Pattern with largest area of same value shows highest correlation 0.75.

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