Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In vivo hyperpolarized ¹³C MRS and metabolic imaging

Abstract

Background & Aims Despite a number of studies addressing the pathophysiology of hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI remains elusive. This study investigated the metabolic alterations in a rat model of hepatic IRI using the in vivo hyperpolarized ¹³C MRS and metabolic imaging. Methods Hyperpolarized 13C MRS with IVIM‐DWI was performed on the liver of 7 sham‐operated control rats and 7 rats before and after hepatic IRI. Results The hepatic IRI‐induced rats showed significantly higher ratios of [1‐13C] alanine/pyruvate, [1‐13C] alanine/tC, [1‐13C] lactate/pyruvate and [1‐13C] lactate/tC compared with both sham‐operated controls and rats before IRI, whereas [1‐13C] pyruvate/tC ratio was decreased in IRI‐induced rats. In IVIM‐DWI study, apparent diffusion coefficient (ADC), f and D values in rats after hepatic IRI were significantly lower than those of rats before IRI and sham‐operated controls. The levels of [1‐13C] alanine and [1‐13C] lactate were negatively correlated with ADC, f and D values, whereas the level of [1‐13C] pyruvate was positively correlated with these values. Conclusions The levels of [1‐13C] alanine, [1‐13C] lactate and [1‐13C] pyruvate in conjunction with IVIM‐DWI will be helpful to evaluate the hepatic IRI as well as these findings can be useful in understanding the biochemical mechanism associated with hepatic damage.

Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

“…Moreover, it has been suggested that acidic anaerobic metabolism results in a perturbed environment that may increase the genetic mutation rate leading to tumor initiation [17]. According to several hyperpolarized 13 C MRS studies [18][19][20][21], [1-13 C] Lac was significantly elevated in hepatic injuries and HCCs, and significantly higher levels of LDH-A were found in HCC than in the normal liver, suggesting that the elevated levels of Lac in HCC can be attributed to the increased LDH-A enzyme level [18]. In our study, serum LDH activity was also positively correlated with the Lac+TG level in patient groups, suggesting that the elevated LDH level could be associated with abnormal Lac metabolism.…”

Metabolic alterations in acute myocardial ischemia-reperfusion injury and necrosis using in vivo hyperpolarized [1-13C] pyruvate MR spectroscopy

“…The rats were housed in an automatic temperature controlled environment with a 12-h light-dark cycle. During surgery, rats were anaesthetized with 2.5–3.0% isoflurane, intubated, and mechanically ventilated at a rate of 60 breaths per minute with a small-animal ventilator (Harvard Rodent Ventilator; Harvard Apparatus, South Natick, MA, USA) 18,19 . Eighteen rats that underwent left thoracotomy without left anterior descending (LAD) coronary artery occlusion were used as sham-operated controls.…”

“…As described previously 18,19 , the rats were anesthetized with 2.5–3% isoflurane mixed with oxygen (1 L/min). A 24-gauge catheter was inserted into the tail vein of each rat for intravenous (IV) administration of the hyperpolarized [1- 13 C] Pyr solution.…”

A variable resolution approach for improved acquisition of hyperpolarized 13C metabolic MRI

“…Hyperpolarization (HP) via dissolution dynamic nuclear polarization 1 overcomes the poor receptivity of 13 C nuclei at clinical field strengths by providing a four to five orders of magnitude increase in signal, enabling dynamic imaging of both the injected substrate and downstream metabolites. Metabolic imaging with hyperpolarized substrates has been used to non-invasively image metabolism in cancer 2 and diabetes, 3 as well as neuroinflammatory disorders 4 and liver 5 and heart disease. 6 It has also shown the potential to both stage disease 7,8 and assess treatment response.…”