Hyperpolarized 13C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model. (14th July 2017)

• Record Type: Journal Article
• Authors: Baligand, Celine; Qin, Hecong; True‐Yasaki, Aisha; Gordon, Jeremy W.; von Morze, Cornelius; Santos, Justin Delos; Wilson, David M.; Raffai, Robert; Cowley, Patrick M.; Baker, Anthony J.; Kurhanewicz, John; Lovett, David H.; Wang, Zhen Jane
• Is Part Of: NMR in biomedicine. Volume 30:Number 10(2017:Oct.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-07-14
• Subjects: Acute kidney injury -- hyperpolarization -- magnetic resonance spectroscopy -- mitochondrial dysfunction -- oxidative stress -- [1−13C]dehydroascorbic acid -- [1−13C]pyruvate; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3765
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13 C dehydroascorbate (DHA) and 13 C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham‐operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13 C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13 C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13 C lactate/pyruvate ratio at day 7 compared with baseline, although the 13 C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham‐operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13 C MRS for the non‐invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI. Abstract : We have shown that hyperpolarized 13 C dehydroascorbate and 13 C pyruvate magnetic resonance spectroscopy can be used to non‐invasively assess the altered renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity following ischemia reperfusion injury in a murine model. Such an imaging approach can potentially enhance the prediction and monitoring of progressive kidney injury.