PURPOSE (1) To evaluate the enhancement patterns of an ultrasmall superparamagnetic iron oxide contrast agent (USPIO-CA) compared with those of a gadolinium-based contrast agent (Gd-BCA). (2) To compare the histologic distribution of USPIO-related iron particles (USPIO-IPs) with the USPIO-enhancement area in the early vascular and in the cellular imaging phase (E- and L-phase, respectively) after intravenous CA administration. METHODS We performed USPIO-enhanced MRI of N-ethyl-N-nitrosourea (ENU)-induced endogenous rat glioma, including spin-echo (SE) T1-weighted images (T1WIs) and gradient-recalled-echo (GRE) T2-weighted images (T2WIs), before and at 3-6 h after USPIO-CA administration for E-phase images. For L-phase images, MRI was performed at 16-19 and 62-69 h after administration. Two observers determined the USPIO-enhancement area on E-phase images and Gd-enhancement areas. We compared the USPIO-enhancement size (USPIO-ES) and Gd-ES on SE T1WIs, and the hypo-intense USPIO-ES on GRE T2WIs and Gd-ES using the Wilcoxon signed-rank test. In addition, two raters visually evaluated the correspondence between the histologic distribution of USPIO-IPs and the USPIO-enhancement area on corresponding GRE T2WIs at each phase using a 3-rating scale. RESULTS Significantly smaller hyper-intense, hypo-intense and combined hyper-/hypo-intense areas were observed on USPIO-enhanced SE T1WIs compared with Gd-enhanced images (all P < 0.001). The hypo-intense USPIO-ES on GRE T2WIs was significantly smaller than the Gd-ES (P = 0.001). The distribution of USPIO-IPs on histopathological specimen and USPIO-enhancement on GRE T2WIs exhibited poor agreement in 5 of 9 tumors with enhancement from rats sacrificed early. The distribution of microglia containing USPIO-IPs corresponded with the pattern of USPIO-enhancement in the 2 tumors with late enhancement. CONCLUSION The enhancement pattern and size of USPIO-CA in a rat glioma model were statistically different from those of Gd-BCA. Our histological data suggests that USPIO-enhanced MRI offers vascular bed imaging in E-phase and might depict the intra-tumoral distribution of immune effector cells in L-phase.
Histologic Distribution and Characteristics on MR Imaging of Ultrasmall Superparamagnetic Iron Oxide in Ethyl-nitrosourea-induced Endogenous Rat Glioma.