Figure 4. DNP-MRS Demonstrates Metabolic Reprogramming in Perfused HCC Cells Surviving Severe Ischemia In Vitro.

(A, B) HCC cells grown under standard growth conditions demonstrated increasing levels of oxygen utilization and associated nucleoside triphosphate to inorganic phosphate (NTP/P_i) ratios, which diminished rapidly when the growth environment is changed to ischemic conditions (anoxia with nutrient depleted medium, single arrow) for 6 hours mimicking TAE. The maintenance of cellular viability under these conditions was underscored by an increase in the oxygen utilization and the NTP/P_i ratio when the oxygen level is increased to 0.017 mM (double arrow). (C, D) DNP-MRS of hyperpolarized 1-¹³C-pyruvate demonstrates metabolic reprogramming of cells surviving TA(C)E-like ischemia (blue spectrum) with a reduction in the alanine to lactate ratio (n=2 injections per condition; p=.023).