Figure 2.

Multimodal data of relaxation rate (R₂), chemical shift imaging (CSI), linewidth (LW), and extracellular pH (pH_e) maps obtained for the same RG2 tumor-bearing rat in Figure 1, which had undergone renal ligation. ((a)(i)–(iv)) represent maps before the SPIO-NPs infusion while ((b)(i)–(iv)) represent the maps after the SPIO-NPs infusion. The R₂ maps were used to delineate and localize the tumor (black outline) and brain (orange outline) boundaries on the CSI, LW, and pH_e maps. R₂ values inside the tumor increased significantly after infusion of SPIO-NPs. The CSI maps were used to create the LW maps and pH_e maps. The LW increased after SPIO-NPs infusion especially in the tumor. The pH_e values within the tumor core and also on the tumor margin were lower than in the healthy/nontumor regions. The panels between the CSI and the LW maps show examples of ¹H spectra of TmDOTP⁵⁻ protons from voxels inside and outside the tumor, revealing a significant intratumoral and peritumoral LW and pH_e difference. A more detailed comparison was done using a region of interest (ROI) analysis of LW ((c)(i)) and pH_e ((c)(ii)) maps before and after the infusion of SPIO-NPs, using the ROI mask shown. The scale bar in the mask denotes 0 to 10 mm diameter circular ROIs (portrayed on a representative rat brain slice). The red dashed line denotes the demarcation between tumor (ROIs 1–3) and tumor edge (ROI 4)/nontumor regions (ROIs 5–9). See Figure S3 for an example of multimodal data of an RG2 tumor rat that underwent coinfusion of probenecid and TmDOTP⁵⁻.