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


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).


CONCLUSIONS
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.
Department of Radiology, University of California, San Francisco 94143-0628, USA.
H
H
Daldrup
D M
DM
Shames
M
M
Wendland
Y
Y
Okuhata
T M
TM
Link
W
W
Rosenau
Y
Y
Lu
R C
RC
Brasch
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D002199:Capillary Permeability; D002273:Carcinogens; D003287:Contrast Media / Q000493:pharmacokinetics; D005038:Ethylnitrosourea; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D002273:Carcinogens; D003287:Contrast Media; D046911:Macromolecular Substances; C058946:albumin-(gadolinium-DTPA); D019786:Gadolinium DTPA; D005038:Ethylnitrosourea