Metabolic MRI With Hyperpolarized 13C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism

Nikolaj Bøgh; Lotte B Bertelsen; Camilla W Rasmussen; Sabrina K Bech; Anna K Keller; Mia G Madsen; Frederik Harving; Thomas H Thorsen; Ida K Mieritz; Esben Ss Hansen; Alkwin Wanders; Christoffer Laustsen

doi:10.1097/RLI.0000000000001094

Metabolic MRI With Hyperpolarized ¹³C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism

Nikolaj Bøgh, Lotte B Bertelsen, Camilla W Rasmussen, Sabrina K Bech, Anna K Keller, Mia G Madsen, Frederik Harving, Thomas H Thorsen, Ida K Mieritz, Esben Ss Hansen, Alkwin Wanders, Christoffer Laustsen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

OBJECTIVES: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized ¹³C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.

MATERIALS AND METHODS: Hyperpolarized ¹³C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13C-pyruvate MRI.

RESULTS: In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13C-pyruvate to 13C-alanine decreased, whereas conversion to 13C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism.

CONCLUSIONS: Our findings demonstrate the promise of hyperpolarized ¹³C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis.

Original language	English
Journal	Investigative Radiology
Volume	59
Issue	12
Pages (from-to)	813-822
Number of pages	10
ISSN	0020-9996
DOIs	https://doi.org/10.1097/RLI.0000000000001094
Publication status	Published - 1 Dec 2024

Keywords

fibrosis
hyperpolarized MRI
kidney disease
metabolic imaging

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Bøgh, N., Bertelsen, L. B., Rasmussen, C. W., Bech, S. K., Keller, A. K., Madsen, M. G., Harving, F., Thorsen, T. H., Mieritz, I. K., Hansen, E. S., Wanders, A., & Laustsen, C. (2024). Metabolic MRI With Hyperpolarized ¹³C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism. Investigative Radiology, 59(12), 813-822. https://doi.org/10.1097/RLI.0000000000001094

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title = "Metabolic MRI With Hyperpolarized 13C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism",

abstract = "OBJECTIVES: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.MATERIALS AND METHODS: Hyperpolarized 13C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13C-pyruvate MRI.RESULTS: In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13C-pyruvate to 13C-alanine decreased, whereas conversion to 13C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism.CONCLUSIONS: Our findings demonstrate the promise of hyperpolarized 13C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis.",

keywords = "fibrosis, hyperpolarized MRI, kidney disease, metabolic imaging",

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Metabolic MRI With Hyperpolarized ¹³C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism. / Bøgh, Nikolaj ; Bertelsen, Lotte B ; Rasmussen, Camilla W et al.
In: Investigative Radiology, Vol. 59, No. 12, 01.12.2024, p. 813-822.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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T1 - Metabolic MRI With Hyperpolarized 13C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism

AU - Bøgh, Nikolaj

AU - Bertelsen, Lotte B

AU - Rasmussen, Camilla W

AU - Bech, Sabrina K

AU - Keller, Anna K

AU - Madsen, Mia G

AU - Harving, Frederik

AU - Thorsen, Thomas H

AU - Mieritz, Ida K

AU - Hansen, Esben Ss

AU - Wanders, Alkwin

AU - Laustsen, Christoffer

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N2 - OBJECTIVES: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.MATERIALS AND METHODS: Hyperpolarized 13C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13C-pyruvate MRI.RESULTS: In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13C-pyruvate to 13C-alanine decreased, whereas conversion to 13C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism.CONCLUSIONS: Our findings demonstrate the promise of hyperpolarized 13C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis.

AB - OBJECTIVES: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.MATERIALS AND METHODS: Hyperpolarized 13C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13C-pyruvate MRI.RESULTS: In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13C-pyruvate to 13C-alanine decreased, whereas conversion to 13C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism.CONCLUSIONS: Our findings demonstrate the promise of hyperpolarized 13C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis.

KW - fibrosis

KW - hyperpolarized MRI

KW - kidney disease

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