Measurement of Rat Brain Tumor Kinetics Using an Intravascular MR Contrast Agent and DCE-MRI Nested Model Selection

Purpose: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters v(p), K-trans, and ve for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not. Materials and Methods: DCE-MRI studies were performed on nine Fisher 344 rats inoculated intracerebrally with 9L gliosarcoma cells using both gadofosveset and gadopentetate. The parameters v(p), K-trans, and v(e) were estimated using NMS. Results: K-trans estimates using gadofosveset, compared to gadopentetate, differed in their means (gadofosveset 0.025 +/- 0.008 min(-1) vs. gadopentetate 0.046 +/- 0.011 min(-1); P = 0.0039). This difference notwithstanding, the intraclass correlation coefficient (ICC) for the two estimates of K trans showed nearly perfect linear dependence (ICC = 0.8479 by Pearson's r). Other estimates, v(e) (gado-fosveset 22.7 6 4.7% v(s). gadopentetate 23.6 6 5.6%; P = 0.4258) and v(p) (gadofosveset 1.5 6 0.5% vs. gadopente-tate 1.6 6 0.4%; P = 0.25), were not different in their means between the two CAs, and there was almost perfect agreement for ve (ICC = 0.8798) and substantial agreement for vp (ICC = 0.7981) between the two CAs. Conclusion: Estimates of K trans were statistically different using gadofosveset and gadopentetate, whereas ve and vp were similar with two CAs. NMS produced robust estimates of pharmacokinetic parameters using DCE-MRI that show promise as important measures of tumor physiology and microenvironment.