Figure 4.

Spatial distributions of compartmentalized ²³Na signals (Na⁺_b, Na⁺_e, Na⁺_i) as well as transendothelial (ΔNa⁺_end) and transmembrane (ΔNa⁺_mem) gradients in an RG2 tumor. The high-resolution ¹H-MRI data are shown in the left four columns, whereas the lower resolution ²³Na-MRSI data are shown in the next five columns on the right. The left column shows the tumor location (white outline) on the anatomical ¹H-MRI (left), whereas the next two columns show the T₂ maps (range shown: 0–100 ms) before and after TmDOTP⁵⁻ injection, and the subsequent column depicts the ∆R₂ map (i.e., difference between 1/T₂ maps before and after, range shown: 0–30 s⁻¹), which is proportional to [TmDOTP^5-] in healthy and tumor tissues. Since ∆R₂ values are more heterogeneous within the tumor, the ²³Na-MRSI data are needed to separate the blood and extracellular compartment signals for the tumor. Since the integral of each ²³Na peak represents the [Na⁺], the respective three columns show the integral maps of Na⁺_b, Na⁺_e, and Na⁺_i from left to right (i.e., ∫Na⁺_b, ∫Na⁺_e, ∫Na⁺_i). The last two columns on the right show ΔNa⁺_end = ∫Na⁺_b-∫Na⁺_e and ΔNa⁺_mem = ∫Na⁺_e-∫Na⁺_i. The ∫Na⁺_b map reveals low values in healthy tissue compared to tumor tissue, and within the tumor boundary a high degree of heterogeneity. The ∫Na⁺_e map reveals low values in tumor and normal tissues, but within the tumor boundary a small degree of heterogeneity is visible while ventricular voxels show very high values. The ∫Na⁺_i map reveals low values ubiquitously except some ventricular voxels. The ΔNa⁺_end map reveals dramatically high values within the tumor only. The ΔNa⁺_end was driven primarily by an increase of ∫Na⁺_b inside the tumor and which was more pronounced in superficial regions of the brain compared to deeper slices. The ΔNa⁺_mem map shows low values in tumor tissue compared to normal tissue, although ventricular voxels show very high values. The ΔNa⁺_mem is driven primarily by decreased ∫Na⁺_e and thus shows similar level of heterogeneity as the ∫Na⁺_e map. All maps use the same color scale and are relative. See Figure S4 for an example for a U87 tumor.