In Vivo Proton Magnetic Resonance Spectroscopy of Hepatic Ischemia/Reperfusion Injury in an Experimental Model

Abstract

Hepatic ischemia/reperfusion injury (IRI) occurs during certain hepatobiliary surgeries, hemorrhagic shock, and veno-occlusive disease. Biochemical changes caused by hepatic IRI lead to hepatocellular remodeling, including cellular regeneration or irreversible apoptosis. This study aims to characterize and monitor the metabolic changes in hepatic IRI using proton magnetic resonance spectroscopy (¹H MRS). Sprague-Dawley rats (n = 8) were scanned with ¹H MRS using 5.0 × 5.0 × 5.0 mm³ voxel over a homogeneous liver parenchyma at 7 Tesla with a respiratory-gated point-resolved spectroscopy sequence at 1 day before, 6 hours, 1 day, and 1 week after 30 minutes total hepatic IRI. Signal integral ratios of choline-containing compounds (CCC), glycogen and glucose complex (Glyu), methylene proton ((-CH₂-)(n)), and methene proton (-CH=CH-) to lipid (integral sum of methyl proton (-CH₃), (-CH₂-)(n) and -CH=CH-) were quantified by areas under peaks longitudinally. The CCC-to-lipid and Glyu-to-lipid ratios at 6 hours after IRI were significantly higher than those at 1 day before, 1 day, and 1 week after injury. The (-CH₂-)(n)-to-lipid, and -CH=CH-to-lipid ratios showed no significant differences over different time points. Hepatocellular regeneration was observed at 6 hours after IRI in histology with immunohistochemical technique. Changes in CCC-to-lipid and Glyu-to-lipid ratios likely reflect the hepatocellular remodeling and impaired glucose utilization upon hepatic IRI, respectively. The experimental findings in the current study demonstrated that ¹H MRS is a valuable tool for characterizing either global or regional metabolic changes in liver noninvasively and longitudinally. Such capability has the potential to lead to early diagnosis and detection of impaired liver function.