Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media

AJR Am J Roentgenol. 1998 Oct;171(4):941-9. doi: 10.2214/ajr.171.4.9762973.


Objective: The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic MR imaging were correlated with histopathologic grade in mammary soft-tissue tumors.

Materials and methods: A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N-ethyl-N-nitrosourea, a potent carcinogen. Dynamic contrast-enhanced MR imaging was performed using a small-molecular contrast medium (gadopentetate, molecular weight = 0.5 kDa) and a macromolecular contrast medium (albumin-(Gd-DTPA)30, molecular weight = 92 kDa) at an interval of 1-2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (K(PS)), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bidirectional kinetic model. MR imaging microvascular characteristics were correlated with histopathologic tumor grade.

Results: Tumor permeability to macromolecular contrast medium, characterized by K(PS), showed a highly positive correlation with tumor grade (r2 = .76, p < 10(-10)). K(PS) values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r2 = .25, p < .003). No correlation between K(PS) or fPV values and tumor grade was found using gadopentetate (r2 = .01, p > .95 and r2 = .03, p > .15, respectively).

Conclusion: Quantitative tumor microvascular permeability assays generated with macromolecular MR imaging contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.

MeSH terms

  • Albumins / pharmacokinetics
  • Animals
  • Capillary Permeability
  • Carcinogens
  • Contrast Media* / pharmacokinetics
  • Ethylnitrosourea
  • Female
  • Gadolinium DTPA / pharmacokinetics
  • Macromolecular Substances
  • Magnetic Resonance Imaging / methods*
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / pathology*
  • Rats
  • Rats, Sprague-Dawley


  • Albumins
  • Carcinogens
  • Contrast Media
  • Macromolecular Substances
  • albumin-(gadolinium-DTPA)
  • Gadolinium DTPA
  • Ethylnitrosourea