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

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Title: Multi‐compartment metabolic assessment of the kidneys by co‐hyperpolarized 13C MRI.
Authors: von Morze, Cornelius1 (AUTHOR) cornelius@wustl.edu, Shaw, Ashley1 (AUTHOR), Shoghi, Kooresh I.1 (AUTHOR), Blazey, Tyler1 (AUTHOR)
Source: Magnetic Resonance in Medicine. Sep2025, Vol. 94 Issue 3, p905-912. 8p.
Subjects: Polarization (Nuclear physics), Biomarkers, Biochemical substrates, Kidney physiology, Kidney diseases
Abstract: 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. [ABSTRACT FROM AUTHOR]
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Abstract: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. [ABSTRACT FROM AUTHOR]
ISSN:07403194
DOI:10.1002/mrm.30568