Figure 4.

(a) (top, left) Pulse sequence diagram of the high-spatial resolution 3D GRASE HP ¹³C MRSI imaging approach used for in vivo HP ¹³C imaging in this study (n and m number of phase encodes and f is the number of frequencies). (a) (top, right) Resonances of [1-¹³C] lactate, [1-¹³C] alanine [1-¹³C] pyruvate, and [¹³C] urea were excited and imaged sequentially as shown for the ¹³C lactate and ¹³C urea phantom. (b) Representative HP ¹³C Lac/Pyr and ¹³C-urea images overlaid on the corresponding T₂-weighted anatomic images for the normal prostate, and low- and high-grade cancer. The color scale of the images represents the magnitude of the Lac/Pyr ratio. (c) Bar graph showing mean ± sdev values for Lac/Pyr, Urea/kidney Urea and Lac/Urea ratio from the normal mouse prostates and low and grade tumors studied. (d) Corresponding mean ± sdev LDH activity values. (e) Corresponding mean ± sdev mRNA expression values of key transporters and enzymes associated with pyruvate and lactate transport and metabolism (Mct1 and Mct4, Ldha and Ldhb) and of factors impacted by the hypoxic tumor microenvironment (Hif1α and Vegf). * denotes p < 0.05, ** for p < 0.005, *** for p < 0.0005.