Multi-compartment metabolic assessment of the kidneys by co-hyperpolarized ¹³C MRI

Purpose: The purpose of this study was to show that hyperpolarized (HP) carbon-13 (¹³C) MRI with multiple co-HP substrates can probe the time course of renal metabolic changes in diabetes. Methods: [1-¹³C]pyruvate and [1,3-¹³C₂]acetoacetate were co-HP for simultaneous metabolic assessment of cytosolic and mitochondrial compartments, respectively. A custom multi-band spectral–spatial radiofrequency pulse was designed for enhanced detection of downstream metabolites of both substrates. In vivo co-HP ¹³C kidney spectra were acquired serially in rats with uncontrolled insulin-deficient diabetes over a period of 8 weeks. Time courses of changes in apparent metabolic conversions of [1-¹³C]pyruvate and [1,3-¹³C₂]acetoacetate were evaluated and compared with routine clinical markers of kidney disease obtained by serum and urine sampling. Results: Metabolic conversions of both co-HP substrates showed large shifts in diabetic kidney with chronic hyperglycemia. Production of both HP [1-¹³C]lactate and [1,3-¹³C₂]β-hydroxybutyrate increased over time, with β-hydroxybutyrate signal significantly elevated at 4 weeks, sustained at 8 weeks. Lactate trended higher at 4 weeks, with a larger, significant increase at 8 weeks. Serum and urine markers of renal function were unaltered from baseline throughout the time course, without significant change in serum creatinine nor evidence of albuminuria. Conclusion: Noninvasive ¹³C MRI using multiple co-HP metabolic substrates, whose activities are localized to distinct cellular compartments, could enable early detection of diabetic kidney damage.