Investigating temporal fluctuations in tumor vasculature with combined carbogen and ultrasmall superparamagnetic iron oxide particle (CUSPIO) imaging

A combined carbogen ultrasmall superparamagnetic iron oxide (USPIO) imaging protocol was developed and applied in vivo in two murine colorectal tumor xenograft models, HCT116 and SW1222, with established disparate vascular morphology, to investigate whether additional information could be extracted from the combination of two susceptibility MRI biomarkers. Tumors were imaged before and during carbogen breathing and subsequently following intravenous administration of USPIO particles. A novel segmentation method was applied to the image data, from which six categories of R₂* response were identified, and compared with histological analysis of the vasculature. In particular, a strong association between a negative ΔR₂*_carbogen followed by positive ΔR₂*_USPIO with the uptake of the perfusion marker Hoechst 33342 was determined. Regions of tumor tissue where there was a significant ΔR₂*_carbogen but no significant ΔR₂*_USPIO were also identified, suggesting these regions became temporally isolated from the vascular supply during the experimental timecourse. These areas correlated with regions of tumor tissue where there was CD31 staining but no Hoechst 33342 uptake. Significantly, different combined carbogen USPIO responses were determined between the two tumor models. Combining ΔR₂*_carbogen and ΔR₂*_USPIO with a novel segmentation scheme can facilitate the interpretation of susceptibility contrast MRI data and enable a deeper interrogation of tumor vascular function and architecture. Magn Reson Med 66:227–234, 2011. © 2011 Wiley‐Liss, Inc.