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 ve 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, ve (gadofosveset 22.7 ± 4.7% vs. gadopentetate 23.6 ± 5.6%; P = 0.4258) and v_p (gadofosveset 1.5 ± 0.5% vs. gadopentetate 1.6 ± 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 v_p (ICC = 0.7981) between the two CAs.

Conclusion: Estimates of K^trans were statistically different using gadofosveset and gadopentetate, whereas ve and v_p 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.