Korean J Radiol.  2011 Dec;12(6):722-730. 10.3348/kjr.2011.12.6.722.

Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

• Ahn SJ
• An CS
• Koom WS
• Song HT
• Suh JS

• KMID: 1101927
• DOI: http://doi.org/10.3348/kjr.2011.12.6.722

Abstract

OBJECTIVE
To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI.
MATERIALS AND METHODS
A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 x 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. RESULTS: Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r = -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep).
CONCLUSION
Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

Keyword

Colorectal cancer; MVD; Nude mouse model; Magnetic resonance imaging; Permeability; Angiogenesis; T1 dynamic contrast enhanced imaging; Ktrans; DLD-1

MeSH Terms

Animals
Capillary Permeability
Colorectal Neoplasms/*blood supply/pathology
*Contrast Media
Female
Gadolinium/diagnostic use
Humans
Image Processing, Computer-Assisted
Immunohistochemistry
*Magnetic Resonance Imaging
Mice
Mice, Nude
Microvessels/*pathology
Neoplasm Transplantation
Neovascularization, Pathologic/diagnosis

Figure

• 

  Fig. 1 Box whisker plot of microvascular density evaluating region of interest drawn on hotspots.Distribution of low and high groups is shown in Ktrans (A) and Kep (B).

• 

  Fig. 2 Representative scatter diagrams showing relationships between microvascular density, necrotic fraction, and dynamic contrast enhanced MRI derived parameters from hotspots.A, B. Ktrans and microvascular density (Spearman's correlation = -0.61, p = 0.06) (A), Kep and microvascular density (Spearman's correlation = -0.60, p = 0.07) (B). Dashed line indicates 95% confidence interval. C. Necrotic fraction and Ktrans (Spearman's correlation = -0.34, p = 0.31). Solid circle represents group that shows low necrotic fraction and high Ktrans. Dashed circle represents group who showed high necrotic fraction and low Ktrans. MVD = microvascular density, NF = necrotic fraction

• 

  Fig. 3 Pixel-by-pixel analysis of Ktrans in tumor of representative mouse #2 evaluated by dynamic contrast enhanced MRI with Tofts model.A. Ktrans values of whole tumor (ROI 1) and hotspot (ROI 2) are 0.285/sec and 0.429/sec, respectively. ROI 1 and ROI 2 are marked by red and green solid lines. B. Hematoxylin and Eosin staining of corresponding section of mouse #2 (original magnification, × 2). Necrosis is noted in center of tumor. C. Hematoxylin and Eosin staining includes hotspot area. Tumor necrosis fraction is 0.03 (original magnification, × 40). Yellow line indicates tumor border and red line indicates area of necrosis. D. CD 31 staining of tumor from mouse #2. Microvascular density count is 53 (original magnification, × 200).

• 

  Fig. 4 Pixel by pixel analysis of Ktrans in tumor of another representative mouse (#10).A. Ktrans values of whole tumors and hotspots were 0.113/sec and 0.237/sec respectively. ROI 1 and ROI 2 are marked by red and green solid lines, respectively. B. Hematoxylin and Eosin staining of corresponding section of mouse #10. Large amount of necrosis is shown (original magnification, × 2). C. Hematoxylin and Eosin staining including hotspot region. Tumor necrotic fraction is 0.31 (original magnification, × 40). Yellow line indicates tumor border and red line indicates area of necrosis. D. CD 31 staining of tissue from mouse #10. Microvascular density count is 108 (original magnification, × 200).

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